Intellectual disability update Jan 2018

Gene: HIST1H4C

Comment when marking as ready: Only two families to date, considered appropriate for amber and watchlist.

Created: 5 Mar 2018, 12:38 p.m.

Added new-gene-name tag, new approved HGNC gene symbol for HIST1H4C is H4C3

Created: 6 Sep 2019, 3:30 p.m. | Last Modified: 6 Sep 2019, 3:30 p.m.

Panel Version: 0.483

This is a probable DD gene in Gene2Phenotype for a HIST1H4C Disease, all missense/in frame variants.

Created: 20 Feb 2018, 3:36 p.m.

Comment on list classification: Currently only two unrelated cases to support HIST1H4C variants causing an observed ID phenotype. There is also animal model in zebrafish that supports the observed phenotype in the patients.

Created: 20 Feb 2018, 3:23 p.m.

added watchlist tag

Created: 20 Feb 2018, 3:12 p.m.

Comment on phenotypes: added phenotypes as listed in PMID:28920961

Created: 20 Feb 2018, 3:12 p.m.

Comment on publications: added publication to support possible association to ID. Tessadori F, et al., 2017 (PMID: 28920961) reported monoallelic missense mutations affecting lysine 91 in the histone H4 core (H4K91) in 2 individuals (3 affecteds) with a syndrome of growth delay, microcephaly and intellectual disability.
The results highlight the alteration of K91 on histone H4 acts in a genetically dominant manner the results suggest a mechanism involving inherent DNA damage accumulation and early perturbation of the cell cycle, through which missense mutations in HIST1H4C affecting K91 of histone H4 are causative for an identifiable syndrome consisting of dysmorphic features and intellectual disability.
They concluded that the presence of two siblings (patients 2 and 3) from unrelated Dutch parents and another independent patient (patient 1) displaying similar clinical phenotypes, in combination with in vivo modeling evidence in zebrafish embryos, indicates that the substitutions affecting the gene HIST1H4C cause the abnormal phenotypes in patients.

Created: 20 Feb 2018, 2:52 p.m.